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Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility

"Double-hit" and "double-expressor" lymphomas represent distinct but overlapping subsets of aggressive B-cell non-Hodgkin lymphoma. The high rates of bone marrow involvement by these lymphomas pose a major therapeutic challenge due to the chemotherapy-resistant nature of the bone...

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Autores principales: Craig, Jeffrey W., Mina, Michael J., Crombie, Jennifer L., LaCasce, Ann S., Weinstock, David M., Pinkus, Geraldine S., Pozdnyakova, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051601/
https://www.ncbi.nlm.nih.gov/pubmed/30020951
http://dx.doi.org/10.1371/journal.pone.0199708
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author Craig, Jeffrey W.
Mina, Michael J.
Crombie, Jennifer L.
LaCasce, Ann S.
Weinstock, David M.
Pinkus, Geraldine S.
Pozdnyakova, Olga
author_facet Craig, Jeffrey W.
Mina, Michael J.
Crombie, Jennifer L.
LaCasce, Ann S.
Weinstock, David M.
Pinkus, Geraldine S.
Pozdnyakova, Olga
author_sort Craig, Jeffrey W.
collection PubMed
description "Double-hit" and "double-expressor" lymphomas represent distinct but overlapping subsets of aggressive B-cell non-Hodgkin lymphoma. The high rates of bone marrow involvement by these lymphomas pose a major therapeutic challenge due to the chemotherapy-resistant nature of the bone marrow microenvironment and the limited utility of rituximab-based salvage regimens in patients with relapsed/refractory disease. Preclinical studies utilizing high-dose cyclophosphamide in combination with the anti-CD52 monoclonal antibody alemtuzumab have recently shown promise in the treatment of intramedullary disease, and a Phase I human trial is now underway. In support of such efforts, here we perform CD52 target validation on a series of double-hit (n = 40) and double-expressor (n = 58) lymphomas using immunohistochemistry. CD52 expression levels varied considerably across samples, however positive staining was observed in 75% of both double-hit and double-expressor lymphomas. Similarly, high levels of CD52 expression were seen in patients whose disease was associated with high-risk clinical features, including primary refractory status (73%), higher IPI score (76%), and bone marrow involvement (74%). CD52 expression was not significantly correlated with diagnostically relevant pathologic features such as morphology, cytogenetic findings or other immunophenotypic features, but was notably present in all cases lacking CD20 expression (n = 6). We propose that CD52 expression status be evaluated on a case-by-case basis to guide eligibility for clinical trial enrollment.
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spelling pubmed-60516012018-07-27 Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility Craig, Jeffrey W. Mina, Michael J. Crombie, Jennifer L. LaCasce, Ann S. Weinstock, David M. Pinkus, Geraldine S. Pozdnyakova, Olga PLoS One Research Article "Double-hit" and "double-expressor" lymphomas represent distinct but overlapping subsets of aggressive B-cell non-Hodgkin lymphoma. The high rates of bone marrow involvement by these lymphomas pose a major therapeutic challenge due to the chemotherapy-resistant nature of the bone marrow microenvironment and the limited utility of rituximab-based salvage regimens in patients with relapsed/refractory disease. Preclinical studies utilizing high-dose cyclophosphamide in combination with the anti-CD52 monoclonal antibody alemtuzumab have recently shown promise in the treatment of intramedullary disease, and a Phase I human trial is now underway. In support of such efforts, here we perform CD52 target validation on a series of double-hit (n = 40) and double-expressor (n = 58) lymphomas using immunohistochemistry. CD52 expression levels varied considerably across samples, however positive staining was observed in 75% of both double-hit and double-expressor lymphomas. Similarly, high levels of CD52 expression were seen in patients whose disease was associated with high-risk clinical features, including primary refractory status (73%), higher IPI score (76%), and bone marrow involvement (74%). CD52 expression was not significantly correlated with diagnostically relevant pathologic features such as morphology, cytogenetic findings or other immunophenotypic features, but was notably present in all cases lacking CD20 expression (n = 6). We propose that CD52 expression status be evaluated on a case-by-case basis to guide eligibility for clinical trial enrollment. Public Library of Science 2018-07-18 /pmc/articles/PMC6051601/ /pubmed/30020951 http://dx.doi.org/10.1371/journal.pone.0199708 Text en © 2018 Craig et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Craig, Jeffrey W.
Mina, Michael J.
Crombie, Jennifer L.
LaCasce, Ann S.
Weinstock, David M.
Pinkus, Geraldine S.
Pozdnyakova, Olga
Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title_full Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title_fullStr Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title_full_unstemmed Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title_short Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
title_sort assessment of cd52 expression in "double-hit" and "double-expressor" lymphomas: implications for clinical trial eligibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051601/
https://www.ncbi.nlm.nih.gov/pubmed/30020951
http://dx.doi.org/10.1371/journal.pone.0199708
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